scholarly journals General Molecular Strategy for Development of Arenavirus Live-Attenuated Vaccines

2015 ◽  
Vol 89 (23) ◽  
pp. 12166-12177 ◽  
Author(s):  
Masaharu Iwasaki ◽  
Nhi Ngo ◽  
Beatrice Cubitt ◽  
John R. Teijaro ◽  
Juan C. de la Torre
Keyword(s):  
Public Health ◽  
Rapid Development ◽  
Hemorrhagic Fever ◽  
Health Problems ◽  
Genome Segment ◽  
Morbidity And Mortality ◽  
High Morbidity ◽  
Major Step ◽  
Live Attenuated Vaccines ◽  
Important Public Health

ABSTRACTHemorrhagic fever arenaviruses (HFA) pose important public health problems in regions where they are endemic. Thus, Lassa virus (LASV) infects several hundred thousand individuals yearly in West Africa, causing a large number of Lassa fever cases associated with high morbidity and mortality. Concerns about human-pathogenic arenaviruses are exacerbated because of the lack of FDA-licensed arenavirus vaccines and because current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. The Mopeia virus (MOPV)/LASV reassortant (ML29) is a LASV candidate live-attenuated vaccine (LAV) that has shown promising results in animal models. Nevertheless, the mechanism of ML29 attenuation remains unknown, which raises concerns about the phenotypic stability of ML29 in response to additional mutations. Development of LAVs based on well-defined molecular mechanisms of attenuation will represent a major step in combatting HFA. We used the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) to develop a general molecular strategy for arenavirus attenuation. Our approach involved replacement of the noncoding intergenic region (IGR) of the L genome segment with the IGR of the S genome segment to generate a recombinant LCMV, rLCMV(IGR/S-S), that was highly attenuatedin vivobut induced protection against a lethal challenge with wild-type LCMV. Attenuation of rLCMV(IGR/S-S) was associated with a stable reorganization of the control of viral gene expression. This strategy can facilitate the rapid development of LAVs with the antigenic composition of the parental HFA and a mechanism of attenuation that minimizes concerns about increased virulence that could be caused by genetic changes in the LAV.IMPORTANCEHemorrhagic fever arenaviruses (HFA) cause high morbidity and mortality, and pose important public health problems in the regions where they are endemic. Implementation of live-attenuated vaccines (LAV) will represent a major step in combatting HFA. Here we have used the prototypic arenavirus LCMV to document a general molecular strategy for arenavirus attenuation that can facilitate the rapid development of safe and effective, as well as stable, LAV to combat HFA.

scholarly journals The High Degree of Sequence Plasticity of the Arenavirus Noncoding Intergenic Region (IGR) Enables the Use of a Nonviral Universal Synthetic IGR To Attenuate Arenaviruses

2016 ◽  
Vol 90 (6) ◽  
pp. 3187-3197 ◽  
Author(s):  
Masaharu Iwasaki ◽  
Beatrice Cubitt ◽  
Brian M. Sullivan ◽  
Juan C. de la Torre
Keyword(s):  
Public Health ◽  
Intergenic Region ◽  
Protective Immunity ◽  
Hemorrhagic Fever ◽  
Health Problems ◽  
Wild Type ◽  
Lethal Challenge ◽  
Important Public Health ◽  
High Degree

ABSTRACTHemorrhagic fever arenaviruses (HFAs) pose important public health problems in regions where they are endemic. Concerns about human-pathogenic arenaviruses are exacerbated because of the lack of FDA-licensed arenavirus vaccines and because current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. We have recently shown that the noncoding intergenic region (IGR) present in each arenavirus genome segment, the S and L segments (S-IGR and L-IGR, respectively), plays important roles in the control of virus protein expression and that this knowledge could be harnessed for the development of live-attenuated vaccine strains to combat HFAs. In this study, we further investigated the sequence plasticity of the arenavirus IGR. We demonstrate that recombinants of the prototypic arenavirus lymphocytic choriomeningitis virus (rLCMVs), whose S-IGRs were replaced by the S-IGR of Lassa virus (LASV) or an entirely nonviral S-IGR-like sequence (Ssyn), are viable, indicating that the function of S-IGR tolerates a high degree of sequence plasticity. In addition, rLCMVs whose L-IGRs were replaced by Ssyn or S-IGRs of the very distantly related reptarenavirus Golden Gate virus (GGV) were viable and severely attenuatedin vivobut able to elicit protective immunity against a lethal challenge with wild-type LCMV. Our findings indicate that replacement of L-IGR by a nonviral Ssyn could serve as a universal molecular determinant of arenavirus attenuation.IMPORTANCEHemorrhagic fever arenaviruses (HFAs) cause high rates of morbidity and mortality and pose important public health problems in regions where they are endemic. Implementation of live-attenuated vaccines (LAVs) will represent a major step to combat HFAs. Here we document that the arenavirus noncoding intergenic region (IGR) has a high degree of plasticity compatible with virus viability. This observation led us to generate recombinant LCMVs containing nonviral synthetic IGRs. These rLCMVs were severely attenuatedin vivobut able to elicit protective immunity against a lethal challenge with wild-type LCMV. These nonviral synthetic IGRs can be used as universal molecular determinants of arenavirus attenuation for the rapid development of safe and effective, as well as stable, LAVs to combat HFA.

scholarly journals Entamoeba histolytica Neglected Tropical Diseases (NTDs) Agents that Infect Humans and Some Other Mammals: A Review

2020 ◽  
Vol 151 ◽  
pp. 01019
Author(s):  
Junaidi Junaidi ◽  
Umi Cahyaningsih ◽  
Trioso Purnawarman ◽  
Hadri Latif ◽  
Etih Sudarnika ◽  
...  
Keyword(s):  
Public Health ◽  
Entamoeba Histolytica ◽  
Search Engines ◽  
Neglected Tropical Diseases ◽  
Morbidity And Mortality ◽  
Google Scholar ◽  
Intestinal Lumen ◽  
High Morbidity ◽  
Tropical Diseases

Amoebiasis caused by Entamoeba histolytica is an important issue in world public health because it is associated with high morbidity and mortality. Entamoeba histolytica is the only species of its genus that commonly causes mild irritation, injury, to inflammation of the walls of the colon and cecum. In some cases, parasites also invade other organs, especially the liver, lungs, kidneys, and brain. Methods: Our article search uses the help of four search engines namely Google Scholar, PubMed, Science Direct, and Springer. Results: Entamoeba histolytica is not easily transmitted from animals to humans, due to the fact that this parasite rarely encysts in the intestinal lumen of animals which is an important factor in the transmission of this parasite. And conversely, subclinical amebiasis in humans acts as the dominant host for transmission of this parasite either from human to human or from human to animal.

scholarly journals Global research on syndemics: A meta-knowledge analysis (2001-2020)

2021 ◽  
Author(s):  
Md Mahbub Hossain ◽  
Nobonita Saha ◽  
Tahmina Tasnim Rodela ◽  
Samia Tasnim ◽  
Tasmiah Nuzhath ◽  
...  
Keyword(s):  
Social Sciences ◽  
Public Health ◽  
Structural Violence ◽  
Rapid Development ◽  
Health Problems ◽  
Health And Wellbeing ◽  
Knowledge Analysis ◽  
Academic Scholarship ◽  
Syndemic Theory ◽  
Multiple Health

Syndemics or synergies of cooccurring epidemics are widely studies across health and social sciences in recent years. We conducted a meta-knowledge analysis of articles published between 2001 to 2020 in this growing field of academic scholarship. We found a total of 830 articles authored by 3025 authors, mostly from high-income countries. Publications on syndemics are gradually increasing since 2003, with rapid development in 2013. Each article was cited more than 15 times on average, whereas most (n = 604) articles were original studies. Syndemics research focused on several areas, including HIV/AIDS, substance abuse, mental health, gender minority stressors, racism, violence, chronic physical and mental disorders, food insecurity, social determinants of health, and COVID-19. Moreover, biopsychosocial interactions between multiple health problems were studied across medical, anthropological, public health, and other disciplines of science. The limited yet rapidly evolving literature on syndemics informs transdisciplinary interests to understand complex coexisting health challenges in the context of systematic exclusion and structural violence in vulnerable populations. The findings also suggest applications of syndemic theory to evaluate clinical and public health problems, examine the socioecological dynamics of factors influencing health and wellbeing, and use the insights to alleviate health inequities in the intersections of synergistic epidemics and persistent contextual challenges for population health.

Agents of Bioterrorism

2012 ◽  
pp. 525-536
Author(s):  
Mark P. Wilhelm
Keyword(s):  
Public Health ◽  
Geographic Area ◽  
Biologic Agents ◽  
Morbidity And Mortality ◽  
High Morbidity ◽  
Public Health Response ◽  
The Public ◽  
Health Response ◽  
Large Geographic Area ◽  
The Cost

Biological agents suitable for use as bioweapons can in many cases be produced and developed in small facilities at relatively modest expense. The human devastation that could be caused by certain biologic agents can rival that of a nuclear device at a small fraction of the cost. Organisms and biotoxins are colorless, odorless, and invisible and have potential for dissemination over a large geographic area. Attacks are difficult to detect before presentation of initial clinical cases. They have the potential to cause high morbidity and mortality, incite panic (creating additional “psychological casualties”). Person-to-person transmission is possible and illness is often difficult to diagnose or treat. The incubation period usually allows escape of the perpetrator. Morbidity and mortality are unpredictable because they vary with agent delivery, environmental conditions, and the public health response. Specific bioterrorism agents and their effects are reviewed.

Tuberculous meningitis in Turkish children: an evaluation of 38 cases

2005 ◽  
Vol 35 (3) ◽  
pp. 183-184 ◽  
Author(s):  
V Ertekin ◽  
H Alp ◽  
S Altinkaynak ◽  
M A Selimogğlu
Keyword(s):  
Public Health ◽  
Tuberculous Meningitis ◽  
Public Health Problem ◽  
Signs And Symptoms ◽  
Morbidity And Mortality ◽  
High Morbidity ◽  
Laboratory Findings ◽  
Turkish Children ◽  
The Past ◽  
Meningitis In Children

Thirty-eight cases of tuberculous meningitis in children were studied. Mortality was 28.9%; most of these presented with stage III disease. Tuberculous meningitis (TBM) still ranks as one of the most important communicable diseases in terms of morbidity and mortality. It is universally fatal if not treated and has high morbidity and mortality, if not recognized early. According to WHO's data, 1.3 million new TB cases under 15 year olds were reported. In Turkey, the TB prevalence is 0.4 %. According to data from the Turkish Ministry of Health, the number of admissions to hospitals dropped from 108 per 100,000 in 1971 to 51 per 10,000 in 1988. Early diagnosis and treatment of TBM are essential in order to prevent late sequelas and death. The diagnosis of TBM may be delayed because many patients initially have vague, seemingly minor, signs and symptoms. In this study, the clinical and laboratory findings of 38 patients with the diagnosis of TBM in our hospital were reviewed, retrospectively, during the past five years. Our purpose was to stress the importance of TBM as a public health problem in Turkey, particularly in the Eastern of Turkey.

A Survey of Antiviral Drugs for Bioweapons

2005 ◽  
Vol 16 (5) ◽  
pp. 283-294 ◽  
Author(s):  
Arthur J. Goff ◽  
Jason Paragas
Keyword(s):  
Public Health ◽  
Disease Control ◽  
National Security ◽  
Significant Risk ◽  
Antiviral Drugs ◽  
Fever Virus ◽  
Morbidity And Mortality ◽  
High Morbidity ◽  
Haemorrhagic Fever ◽  
Chemical Structures

Smallpox (variola major), and the haemorrhagic fever viruses (filoviruses and arenaviruses) are classified as Category A biowarfare agents by the Centers for Disease Control. Category A agents pose a significant risk to public health and national security because they can be easily disseminated by aerosol, although with the exception of variola, they are not easily transmitted from person to person. An attack with these viruses would result in high morbidity and mortality and cause widespread panic. With the exception of smallpox and Argentine haemorrhagic fever virus, there are no vaccines or approved treatments to protect against these diseases. In this review we focus on promising prophylactic, therapeutic and disease modulating drugs (see Figure 1 for select chemical structures).

scholarly journals Blocking HTLV-1/2 silent transmission in Brazil: Current public health policies and proposal for additional strategies

2021 ◽  
Vol 15 (9) ◽  
pp. e0009717
Author(s):  
Carolina Rosadas ◽  
Maria Luiza B. Menezes ◽  
Bernardo Galvão-Castro ◽  
Tatiane Assone ◽  
Angélica E. Miranda ◽  
...  
Keyword(s):  
Public Health ◽  
T Cell ◽  
Morbidity And Mortality ◽  
Health Policies ◽  
Curative Treatment ◽  
High Morbidity ◽  
Public Health Policies ◽  
The Public ◽  
Brazil Current ◽  
Human T Cell

Human T-cell lymphotropic viruses 1 and 2 (HTLV-1/2) are relatively common in Brazil but remain silent and neglected infections. HTLV-1 is associated with a range of diseases with high morbidity and mortality. There is no curative treatment for this lifelong infection, so measures to prevent transmission are essential. This narrative review discusses HTLV-1/2 transmission routes and measures to prevent its continuous dissemination. The public health policies that are currently implemented in Brazil to avoid HTLV-1/2 transmission are addressed, and further strategies are proposed.

scholarly journals Use of Graph Theory to Identify Patterns of Deprivation and High Morbidity and Mortality in Public Health Data Sets

2005 ◽  
Vol 12 (6) ◽  
pp. 630-641 ◽  
Author(s):  
Peter A. Bath ◽  
Cheryl Craigs ◽  
Ravi Maheswaran ◽  
John Raymond ◽  
Peter Willett
Keyword(s):  
Public Health ◽  
Graph Theory ◽  
Health Data ◽  
Morbidity And Mortality ◽  
High Morbidity ◽  
Data Sets ◽  
Public Health Data

scholarly journals 1656. Klebsiella pneumoniae Antimicrobial Susceptibility to Carbapenems in Latin America Between 2000 and 2014

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S605-S606
Author(s):  
Hatim Sati ◽  
Nienke Bruinsma ◽  
Jenny Hsieh ◽  
Marcelo F Galas ◽  
Pilar Ramon-Pardo
Keyword(s):  
Public Health ◽  
Latin America ◽  
Klebsiella Pneumoniae ◽  
Antimicrobial Susceptibility ◽  
Treatment Options ◽  
Morbidity And Mortality ◽  
Health Concern ◽  
High Morbidity ◽  
Percentage Increase ◽  
Rate Of Increase

Abstract Background Antimicrobial resistance (AMR) to carbapenems in Enterobacteriaceae such as Klebsiella pneumoniae (KPN) is a major global public health concern. Infections caused by these pathogens are associated with high morbidity and mortality and perpetuated by limited safe alternative treatment options. This study aims to describe the antimicrobial susceptibility patterns amongst KPN to the carbapenems Latin America. Methods Surveillance laboratory data from 2000 to 2014 were obtained through the ReLAVRA network from 19 countries in Latin America. Longitudinal trends of mean percentage non-susceptibility for the region were conducted and evaluated with a significance level of P < 0.05. Results A total of 209,972 and 181,128 KPN isolates were reported from 2000 to 2014 for antibiotic susceptibility to imipenem and meropenem, respectively. From 2000 to 2014 an increasing trend was observed in the reported % KPN NS to imipenem (P < 0.0001) from 0.6% to 11.6% with an average annual percentage increase (AAPI) of 36.3% [95% CI: 39.8%–33%]. (Figure 1). Similarly, the % KPN NS to meropenem increased (P < 0.0001) from 0% in 2000 to 12.3% in 2014 with an AAPI of 49.5% [95% CI: 54%–44.6%] (Figure 2). For both antibiotics, the last 5 years of the timeframe (2010 to 2014) showed the highest rate of increase in NS. NS to carbapenems varied significantly between reporting countries, with the highest % KPN NS to imipenem and meropenem reported by Brazil, Guatemala, Nicaragua, and Peru. Conclusion The increase in KPN NS to carbapenems observed in Latin America threatens effective treatment of infections caused by this pathogen. The extremely limited treatment options could lead to further increases in morbidity and mortality. Strengthening health systems and core country capacity to identify and deal with these emerging high-risk pathogens and resistance mechanisms, through surveillance is vital to inform public health actions, control measures, mitigate outbreaks and support further development of Public health actions against AMR at country and regional level. Disclosures All authors: No reported disclosures.

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